The existence of calretinin was studied in the rat intestinal system and dorsal root ganglion. The stomach, duodenum, ileum, jejunum, colon and caecum from rats were examined using immunofluorescence to detect the presence of calretinin (CR) positive cells and fibers. In addition, the presence or absence of calcitonin gene related peptide (CGRP), which is frequently associated with sensory neurons was investigated, using colocalization immunofluorescence in order to elucidate the function of calretinin. CR+ cell bodies and fibers were found throughout the extent of the gastrointestinal system in the Auerbach's and Meissner's plexus. The presence of CR mRNA was confirmed with in situ hybridization in these cells. Fine CR+ fibers were found in both plexuses as well as in the circular and longitudinal muscle layers. Of particular interest was the presence of CR+fibers in the villi of the intestinal system. These fibers reach from the base to the tip of the villi and are colocalized with CGRP but are not limited to only innervation of blood vessels. Occasional CR positive cells were found scattered throughout the villus as visualized by in situ hybridization. As the possibility existed that the CGRP+/CR+ fibers originated in the dorsal root ganglion, we examined cells in this area for colocalization. While colocalization did exist, the levels were quite low. The colocalization of CR and CGRP in the same fibers in the villus suggests a sensory role for the protein. The role of CR is still unclear, but the continued examination of the protein and its colocalization with other neuropeptides may yield information into its function.